# Peroxisomes in Aging: Guardians of Cellular Resilience and Function

## TL;DR

Peroxisomes decline with age, causing cellular stress and dysfunction, and maintaining their health could help prevent age-related diseases.

## Contribution

The paper highlights peroxisomes as central hubs in aging and identifies them as emerging therapeutic targets for age-related diseases.

## Key findings

- Aging impairs peroxisomal functions like lipid metabolism and redox balance.
- Peroxisomal dysfunction spreads stress to other organelles like mitochondria and lysosomes.
- Maintaining peroxisomal homeostasis supports healthy aging and metabolic stability.

## Abstract

What are the main findings?
Peroxisomal functions decline with age, impairing protein import, lipid metabolism, redox balance, and organelle quality control.Peroxisomes act as central signaling hubs, and their dysfunction propagates stress to mitochondria, the endoplasmic reticulum, and lysosomes.

Peroxisomal functions decline with age, impairing protein import, lipid metabolism, redox balance, and organelle quality control.

Peroxisomes act as central signaling hubs, and their dysfunction propagates stress to mitochondria, the endoplasmic reticulum, and lysosomes.

What are the implications of the main findings?
Peroxisomal homeostasis supports healthy aging by contributing to cellular resilience and metabolic stability.Peroxisomal pathways are emerging as therapeutic targets for age-related diseases and functional decline.

Peroxisomal homeostasis supports healthy aging by contributing to cellular resilience and metabolic stability.

Peroxisomal pathways are emerging as therapeutic targets for age-related diseases and functional decline.

Peroxisomes are multifunctional organelles that play essential roles in lipid metabolism, redox regulation, and cellular signaling. An expanding body of evidence implicates peroxisomal dysfunction as a key contributor to aging and age-related diseases. Aging is accompanied by progressive declines in key peroxisomal functions, including catalase activity, fatty acid β-oxidation, plasmalogen biosynthesis, and the metabolism of bile acids and docosahexaenoic acid, resulting in increased oxidative stress, lipid dysregulation, and alterations in membrane composition. Impaired pexophagy further exacerbates these defects by allowing the accumulation of damaged peroxisomes and compromising cellular homeostasis. Through extensive metabolic and signaling crosstalk with mitochondria, the endoplasmic reticulum, and lysosomes, peroxisomal dysfunction can propagate oxidative and metabolic disturbances throughout the cell. In addition, peroxisome-derived signaling molecules, such as hydrogen peroxide and bioactive lipids, link peroxisomal activity to cellular stress responses and organismal metabolic homeostasis. We propose that aging-associated impairments in peroxisomal protein import, redox regulation, and selective turnover progressively shift peroxisomes from adaptive metabolic signaling hubs toward sources of chronic oxidative and lipid stress. In this context, current studies highlight peroxisomal homeostasis as a potential determinant of healthy aging and point to peroxisomal pathways as emerging targets for intervention in age-related disease.